Why Does Zantac Contain NDMA and Can’t They Purify It?

Did you know that the popular Zantac, also known by its generic name Ranitidine, has recently come under scrutiny due to the presence of a potential carcinogen? Specifically, N-nitrosodimethylamine (NDMA) has been detected in several batches of the drug. This article delves into the reasons behind the contamination, the testing process, and the ongoing investigation.

The Contamination of NDMA in Zantac

NDMA is a suspected human carcinogen. In 2019, the U.S. Food and Drug Administration (FDA) received a petition from Valisure, a citizen science organization, which had found unexpected levels of NDMA in samples of Zantac through their own testing methods. Valisure used a gas chromatography (GC) method, which can sometimes lead to the formation of NDMA due to degradation during the process.

Timeline of Events

The following timeline highlights key developments in the investigation of Zantac and NDMA:

September 9, 2019: Valisure petitioned the FDA, reporting unexpectedly high levels of NDMA in samples of Zantac. September 13, 2019: The FDA issued a statement informing the public about the detection of NDMA in samples of ranitidine. September 18, 2019: Sandoz (a division of Novartis AG) halted the distribution of Zantac as a precautionary measure. September 19, 2019: Some European Union countries, such as Germany, initiated recalls of Zantac due to a potentially contaminated active pharmaceutical ingredient (API) manufactured by Saraca Laboratories Ltd. September 20, 2019: Dr. Reddy’s Laboratories Ltd. also suspended the distribution of Zantac as a precaution. September 24, 2019: The FDA announced a voluntary recall of 14 lots of Sandoz ranitidine capsules after detecting impurities. September 26, 2019: The FDA initiated a voluntary recall of Zantac manufactured by Apotex Corp. October 2, 2019: The FDA updated the testing methods for detecting NDMA impurities, recommending the use of LC-HRMS over GC to prevent NDMA formation during testing.

Understanding the Testing Process

The initial testing methods used by Valisure involved gas chromatography (GC), which can lead to the formation of NDMA during the process. This led to preliminary findings of 3 mg of NDMA per tablet. However, these results are now understood to be related to the degradation of the samples during testing rather than an inherent issue with the drug itself. Other studies, such as the 2016 article by Cohn and colleagues, suggest that ranitidine can form NDMA in the body under certain conditions.

The Role of Manufacturing and Stomach Conditions

Several factors might contribute to the presence of NDMA in Zantac:

Manufacturing issues: There is a possibility that some manufacturers are incorporating NDMA into their product due to changes in their manufacturing processes. Stomach conditions: Ranitidine, which has a nitrite functional group, can react with nitrite present in the stomach to form NDMA.

Valisure conducted tests using simulated gastric fluid and added sodium nitrite, a component present in some foods and produced by certain bacteria. They found that even with 25 mM sodium nitrite, they could detect 23600 ng per tablet of NDMA. This suggests that NDMA can form from ranitidine under stomach conditions, regardless of its initial presence in the tablet.

In addition, a 2016 study by Cohn and colleagues found a 400-fold increase in urinary NDMA concentrations after ranitidine consumption, indicating that NDMA can be formed within the body.

What Consumers Should Do

As a precaution, consumers should avoid Zantac until the investigation is complete. Healthcare professionals should consider alternative treatments for those currently using Zantac. However, it's important to note that while the presence of NDMA is concerning, the benefits of ranitidine for some medical conditions may outweigh the risks. Therefore, any decision to switch medications should be made in consultation with a healthcare professional.

Conclusion and Ongoing Investigation

While the investigation into the presence of NDMA in Zantac is ongoing, it is clear that this issue is complex and multifaceted. It involves both manufacturing and testing processes, as well as potential reactions within the body. The FDA and other medical agencies are working to thoroughly investigate this issue and take appropriate action.

As always, the goal is to balance the risks against the benefits of any medication. Stay informed and consult with your healthcare provider for the best course of action.